We used our humanized mouse model to investigate the therapeutic effects of interferon alpha subtype 14 against HIV infection in vivo. We previously showed that human IFN-alpha14 subtype had potent anti-HIV activity, and was much stronger than the IFN-alpha2 subtype, which is currently in HIV-1 clinical trials. We used our TKO_BLT-humanized mouse model to test the efficacy of IFN-alpha14 in treatment of latent HIV infections when combined with oral combination antiretroviral therapy. The animal experiments have been completed and a manuscript describing the results has been submitted. The combination of antiretroviral drugs and IFNa14 reduced virus loads but did not cure the infections.. It is important to understand how the latent reservoir of HIV-1 becomes established because it is the latent virus that becomes reactivated if antiretroviral therapy is interrupted. In collaboration with Warner Greene at the Gladstone Institute we have completed animal experiments to determine if CCR2+/CCR5+ CD4+ T cells are the main reservoirs of virus. Samples from the animals are being evaluated for HIV-1 RNA and DNA levels by our collaborator, Ulf Dittmer. Experiment testing the efficacy of anti-CD47 immunotherapy in HIV-1-infected humanized mice produced evidence that anti-CD47 could reduce HIV-1 virus loads in established infections. We are unable to follow up on these results, replicate them and determine the mechanisms of action of anti-CD47 because of the Executive Order banning intramural scientists from using fetal tissue in research. A manuscript containing the preliminary results has been submitted.